The Research Center for Alcoholic Liver and Pancreatic Diseases is the first and only Los Angeles city-wide Research Center of Excellence devoted to "Elucidation of the mechanisms by which ethanol primes and sensitizes the liver and pancreas for injury". Since its inception in 1999, it has increased the member roster from 9 to 32 and has directly contributed to a growth of NIAAA/NIH-funded alcohol research among the center members to total annual direct costs in excess of $3.4 million. In addition, the Center has achieved new and interactive programmatic developments in undergraduate/graduate/postdoctoral education and training, non-parenchymal liver cell isolation core, cirrhosis research program, epidemiology and prevention program, clinical research, and public outreach program, and this is the basis for the current proposal for a comprehensive research center. Our Center is unique in supporting two distinct basic science approaches. One is addition and deletion analysis for genetic understanding of predisposition to alcoholic liver and pancreatic diseases (ALPD), the approach that is facilitated by the use of the mouse intragastric ethanol infusion model provided by the Center's Animal Core. Another is cell-type specific research to support delineation of the priming and sensitizing mechanisms in each parenchymal and non-parenchymal liver cell types and understanding of complex cellular cross talks that are central to evolution of ALPD. This is supported by the Center's Non-Parenchymal Liver Cell Core separately funded by a NIAAA R24 grant and effective collaborations with the NIDDK-supported USC Liver Center's Cell Culture Core. Further, our Center takes a pride in having these two powerful but technically challenging approaches available to alcohol researchers across the nation via their utilization of the Animal and Non-Parenchymal Liver Cell Cores. The Center is also committed to disseminating new information generated from basic, epidemiological, and clinical research and to developing and implementing educational prevention programs for alcoholic liver disease. These programs are specifically tailored for and targeted to identified high risk groups in our community that incur the most serious medical and socioeconomic impacts from the disease. It is our Center's ultimate goal to promote cutting-edge science on the predisposition mechanisms, to bridge it to the bedside and people in the community, and to help combat the diseases.